scholarly journals Differences in Expression of Mitochondrial Complexes Due to Genetic Variants May Alter Sensitivity to Radiation-Induced Cardiac Dysfunction

2020 ◽  
Vol 7 ◽  
Author(s):  
Rachel A. Schlaak ◽  
Anne Frei ◽  
Gopika SenthilKumar ◽  
Shirng-Wern Tsaih ◽  
Clive Wells ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Cardiac Dysfunction ◽  
Radiation Induced ◽  
Mitochondrial Complexes

scholarly journals Genetic Variants of DNA Repair Genes as Predictors of Radiation-Induced Subcutaneous Fibrosis in Oropharyngeal Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Ankita Gupta ◽  
Don Mathew ◽  
Shabir Ahmad Bhat ◽  
Sushmita Ghoshal ◽  
Arnab Pal
Keyword(s):  
Dna Repair ◽  
Genetic Variants ◽  
Oropharyngeal Carcinoma ◽  
Dna Repair Genes ◽  
Nucleotide Polymorphisms ◽  
Radical Radiotherapy ◽  
Single Nucleotide ◽  
Radiation Induced ◽  
Repair Genes ◽  
Severe Fibrosis

PurposeTo investigate the impact of genetic variants of DNA repair and pro-fibrotic pathway genes on the severity of radiation-induced subcutaneous fibrosis in patients of oropharyngeal carcinoma treated with radical radiotherapy.Materials and MethodsPatients of newly diagnosed squamous cell carcinoma of oropharynx being treated with two-dimensional radical radiotherapy were enrolled in the study. Patients who had undergone surgery or were receiving concurrent chemotherapy were excluded. Patients were followed up at 6 weeks post completion of radiotherapy and every 3 months thereafter for a median of 16 months. Subcutaneous fibrosis was graded according to the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) grading system and the maximum grade was recorded over the length of the patient’s follow-up. Patients with severe fibrosis (≥G3), were compared to patients with minor (≤G2) fibrotic reactions. Eight single nucleotide polymorphisms of 7 DNA repair genes and 2 polymorphisms of a single pro-fibrotic pathway gene were analyzed by Polymerase Chain Reaction and Restriction Fragment Length Polymorphism and were correlated with the severity of subcutaneous fibrosis.Results179 patients were included in the analysis. Subcutaneous fibrosis was seen in 168 (93.9%) patients. 36 (20.1%) patients had severe (grade 3) fibrosis. On multivariate logistic regression analysis, Homozygous CC genotype of XRCC3 (722C>T, rs861539) (p=0.013*, OR 2.350, 95% CI 1.089-5.382), Homozygous AA genotype of ERCC4 Ex8 (1244G>A, rs1800067) (p=0.001**, OR 11.626, 95% CI 2.490-275.901) and Homozygous TT genotype of XRCC5 (1401G>T, rs828907) (p=0.020*, OR 2.188, 95% CI 1.652-7.334) were found to be predictive of severe subcutaneous fibrosis. On haplotype analysis, the cumulative risk of developing severe fibrosis was observed in patients carrying both haplotypes of variant Homozygous AA genotype of ERCC4 Ex8 (1244G>A, rs1800067) and Homozygous TT genotype of XRCC5 (1401 G>T, rs828907) (p=0.010*, OR 26.340, 95% CI 4.014-76.568).ConclusionWe demonstrated significant associations between single nucleotide polymorphisms of DNA repair genes and radiation-induced subcutaneous fibrosis in patients of oropharyngeal carcinoma treated with radiotherapy. We propose to incorporate these genetic markers into predictive models for identifying patients genetically predisposed to the development of radiation-induced fibrosis, thus guiding personalized treatment protocols.

scholarly journals PO-0904: Genetic variants in apoptosis-related genes and radiation-induced late toxicity in prostate cancer patients

2013 ◽  
Vol 106 ◽  
pp. S350
Author(s):  
T. Langsenlehner ◽  
E.M. Thurner ◽  
W. Renner ◽  
K.S. Kapp ◽  
U. Langsenlehner
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Genetic Variants ◽  
Late Toxicity ◽  
Radiation Induced

scholarly journals Chemotherapy-Related Cardiac Dysfunction

2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Marijke Linschoten ◽  
Arco J. Teske ◽  
Maarten J. Cramer ◽  
Elsken van der Wall ◽  
Folkert W. Asselbergs
Keyword(s):  
Risk Factors ◽  
Risk Stratification ◽  
Genetic Variants ◽  
Cardiac Dysfunction ◽  
Genetic Risk ◽  
Drug Transport ◽  
Association Studies ◽  
Genetic Risk Factors ◽  
Candidate Gene Approach ◽  
Genome Wide Association Studies

Chemotherapy-related cardiac dysfunction is a significant side effect of anticancer treatment. Risk stratification is based on clinical- and treatment-related risk factors that do not adequately explain individual susceptibility. The addition of genetic variants may improve risk assessment. We conducted a systematic literature search in PubMed and Embase, to identify studies investigating genetic risk factors for chemotherapy-related cardiac dysfunction. Included were articles describing genetic variants in humans altering susceptibility to chemotherapy-related cardiac dysfunction. The validity of identified studies was assessed by 10 criteria, including assessment of population stratification, statistical methodology, and replication of findings. We identified 40 studies: 34 exploring genetic risk factors for anthracycline-induced cardiotoxicity (n=9678) and 6 studies related to trastuzumab-associated cardiotoxicity (n=642). The majority (35/40) of studies had a candidate gene approach, whereas 5 genome-wide association studies have been performed. We identified 25 genetic variants in 20 genes and 2 intergenic variants reported significant at least once. The overall validity of studies was limited, with small cohorts, failure to assess population ancestry and lack of replication. SNPs with the most robust evidence up to this point are CELF4 rs1786814 (sarcomere structure and function), RARG rs2229774 (topoisomerase-2β expression), SLC28A3 rs7853758 (drug transport), UGT1A6 rs17863783 (drug metabolism), and 1 intergenic variant (rs28714259). Existing evidence supports the hypothesis that genetic variation contributes to chemotherapy-related cardiac dysfunction. Although many variants identified by this systematic review show potential to improve risk stratification, future studies are necessary for validation and assessment of their value in a diagnostic and prognostic setting.

scholarly journals OC-0485: Genetic variants associated with radiation-induced morbidity in a head-and neck cancer cohort

2018 ◽  
Vol 127 ◽  
pp. S249-S250
Author(s):  
L.M.H. Schack ◽  
L. Dorling ◽  
L. Fachal ◽  
C. Luccarini ◽  
A.M. Dunning ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Genetic Variants ◽  
Radiation Induced

scholarly journals Molecular characterization of a radiation-induced reverse mutation at the dilute locus in the mouse

1987 ◽  
Vol 50 (3) ◽  
pp. 219-223 ◽  
Author(s):  
Jack Favor ◽  
P. Günter Strauss ◽  
Volker Erfle
Keyword(s):  
Homologous Recombination ◽  
Mutation Rate ◽  
Genetic Variants ◽  
Mouse Genome ◽  
Mutagenic Treatment ◽  
Proviral Sequence ◽  
Leukaemia Virus ◽  
Reverse Mutation ◽  
Radiation Induced

SummaryIrradiation has been employed successfully to increase the reverse mutation rate at the agouti and dilute loci in the mouse. The dilute allele has previously been shown to be due to the insertion of an ecotropic-specific murine leukaemia virus in the vicinity of the dilute locus, and its instability to be due to the excision of the proviral sequence (Jenkinset al.1981). Molecular analysis of the recovered radiation-induced revertant at the dilute locus indicated excision of all but approximately 500 bp of the proviral sequence. The proviral sequence remaining in the mouse genome hybridizes to a probe specific for the proviral long terminal repeat (LTR) sequence. Previous characterization of two spontaneous reverse dilute mutations indicated precise proviral excision of all but a single LTR, and suggests homologous recombination between the proviral LTR sequences as the mechanism of proviral excision (Hutchison, Copeland & Jenkins 1984). The present results indicate that radiation and increases the reverse mutation rate at the dilute locus acts by a similar mechanism, and suggest that mutagenic treatment may be employed to produce genetic variants of interest.

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